We report the characteristics and electrochemical sensing features of iron-tetrasulfophthalocyanine (FeTSPc)-functionalized graphene nanosheets (GNs) composites. The noncovalently FeTSPc-functionalized GNs (GNs–FeTSPc) possess an improved solubility in aqueous solution and the GNs–FeTSPc film electrode exhibits an enhanced electrocatalytic activity towards oxidation of isoniazid (INZ) and uric acid (UA). Direct electrochemistry of GNs–FeTSPc nanocomposites shows that GNs could facilitate the electron transfer between glass carbon electrodes (GCEs) and the electroactive center of FeTSPc. Additionally, a comparative study using different carbon nanomaterials reveals that the functionalized GNs have better electrocatalytic ability than that of multi-walled carbon nanotubes (MWCNTs) and graphite while no obvious enhancement is obtained on mesoporous carbons (MPC) and fullerene (C60). Hence, the GNs with unusual structure are suitable for preparing functionalized nanocomposite as a promising electrochemical sensing platform.